It is estimated that almost one-third of adverse reactions to pharmaceutical agents result from drug interactions. The potential for drug interactions in oncology complicates the pharmacist's role of finding a balance between efficacy and acceptable toxicity for all agents involved (anticancer agents, supportive therapies, and concomitant medications). In the realm of metastatic breast cancer, the heavily pretreated nature of many patients and the narrow therapeutic window associated with most therapies puts all patients at risk for drug interactions. In practice, co-administration of a pharmacological agent with the potential to alter the clinical profile of the patient's anticancer regimen may be unavoidable. Herein are discussed underlying molecular mechanisms that are usually responsible for drug interactions in the realm of breast oncology. Since more and more oral anticancer agents are emerging onto the market or are in late clinical development, special consideration is given to identification and management of potential interactions associated with oral anticancer therapeutics. In addition, recommendations are provided for dose reduction strategies, effective monitoring, management of drug interactions, and communication strategies with patients and other members of the clinical team.